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Biomedical subjects

K L Cheung

Publications and source records attributed to K L Cheung.

At least 19 recordsLinked to original sources
PubMed2006

How relevant is breast cancer screening in the Asia/Pacific region?

Nationwide breast cancer screening with mammography is well-established in many western countries. Many studies have shown its benefit in mortality reduction. However, breast cancer screening in Asia has been slow to implement, as it was perceived that the breast cancer incidence was low and the parenchyma of Asian women was difficult to assess mammographically. With changing disease patterns, breast cancer is now one of the most common cancers amongst women in Asia. Breast cancer screening has become an important and relevant health problem. However, apart from biological differences between western and Asian women, cultural and economic considerations need to be addressed. This paper looks at the various issues pertaining to the feasibility and relevance of population-based screening in the Asia/Pacific region.

Asia↗
PubMed2006

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents.

BACKGROUND: High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. PATIENTS AND METHODS: According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. RESULTS: Twelve patients with a median age of 75.1 years (49.1-85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3rd to 7th line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for > or = 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7-36) months. The time to treatment failure was 4 (0.5-36) months. CONCLUSION: Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy.

Journal Article↗
PubMed2006

Deletion of chromosome 13 detected by conventional cytogenetics is a critical prognostic factor in myeloma.

In myeloma, the prognostic impact of different strategies used to detect chromosome 13 deletion (Delta13) remains controversial. To address this, we compared conventional cytogenetics and interphase fluorescence in situ hybridization (iFISH) in a large multicenter study (n=794). The ability to obtain abnormal metaphases was associated with a poor prognosis, which was worse if Delta13, p53 deletion or t(4;14) was present, but only Delta13 remained significant on multivariate analysis. Patients with Delta13, by either cytogenetics or iFISH, had a poor prognosis. However, when cases with Delta13 detectable by both cytogenetics and iFISH were separated from those detected by iFISH only, the poor prognosis of iFISH-detectable Delta13 disappeared; their outcome matched that of patients with no detectable Delta13 (P=0.115). Addition of ploidy status to iFISH-Delta13 did not affect the prognostic value of the test. Indeed both cytogenetics and iFISH Delta13 divided both hyperdiploidy and nonhyperdiploidy into two groups with similar prognoses, indicating that the poor prognosis of ploidy is entirely due to its association with Delta13. We conclude that Delta13 detected by metaphase analysis is a critical prognostic factor in myeloma. Absence of Delta13, even in those patients yielding only normal or no metaphases, is associated with a relatively good prognosis.

Adult↗
PubMed2006

"Resurrection of clinical efficacy" after resistance to endocrine therapy in metastatic breast cancer.

BACKGROUND: In a significant proportion of metastatic breast cancer (MBC) patients whose tumour has progressed within 6 months of endocrine therapy (de novo resistance), it is generally believed that the chance of achieving clinical benefit (CB) with further endocrine therapy is minimal. METHODS: Data was retrieved from a prospectively updated database of metastatic breast cancer. Relevant data was exported to SPSS software for statistical analysis. RESULTS: In oestrogen receptor (ER) positive MBC patients with assessable disease, CB was achieved in 159 (71.3%) (1st line) patients. When these patients were put on further endocrine therapy, the CB rates were 63.2% (on 2nd line), 46.1% (on 3rd line) and 20% (on 4th line) with a median duration of response (DOR) in those with CB of 22, 12, 11 and 15 months respectively. The remaining 64 (28.7%) patients had de novo resistance on 1st line endocrine therapy. Seventeen of these patients were treated with further endocrine therapy. The CB rates were 29.4% (on 2nd line) and 22.2% (on 3rd line) with a median DOR in those with CB of 22.7 months and 14 months respectively. CONCLUSION: The chance of further endocrine response continues to decrease with each line of therapy, yet CB is still seen with reasonable duration even with a 4th line agent. In addition, further endocrine response, with long duration, can be seen in a significant proportion of patients who have developed de novo resistance to 1st line endocrine therapy. The use of further endocrine therapy should not be excluded under these circumstances.

Journal Article↗
PubMed2006

Endocrine response after prior treatment with fulvestrant in postmenopausal women with advanced breast cancer: experience from a single centre.

The pure anti-oestrogen fulvestrant has now been licensed for use in advanced breast cancer which has progressed on an anti-oestrogen. Optimal sequencing of various endocrine agents becomes very important in the therapeutic strategy. We report our experience of further endocrine response with another endocrine agent after prior fulvestrant treatment. Among all patients with advanced breast cancer who had been entered into five phase II/III trials using fulvestrant as first- to ninth-line endocrine therapy in our Unit since 1993, 54 patients who fulfilled the following criteria were studied for their subsequent endocrine response: (i) oestrogen receptor positive or unknown; (ii) having been on a subsequent endocrine therapy for > or =6 months unless the disease progressed before; and (iii) with disease assessable for response according to International Union Against Cancer criteria. Eleven patients had received an aromatase inhibitor prior to fulvestrant, which resulted in five CBs (clinical benefit = objective remission/stable disease (SD)) for > or =6 months). Twenty-eight patients achieved CB on fulvestrant. They went on subsequent endocrine therapy with two partial responses, 11 SDs and 15 PDs (progressive disease) at 6 months. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 46.6 and 18.2 months. Among the remaining 26 patients who progressed at 6 months on fulvestrant, there were three SDs and 23 PDs at 6 months on subsequent endocrine therapy. The median survival from starting fulvestrant and subsequent endocrine therapy was respectively 12.5 and 9.3 months. Of all these 54 patients, 30% (n = 16) therefore achieved CB using another (second- to tenth-line) endocrine agent (anastrozole = 26; tamoxifen = 12; megestrol acetate = 11; others = 5). It would thus appear that further endocrine response can be induced in a reasonable proportion of patients after failing fulvestrant.

Adult↗
PubMed2006

Nasal glioma.

Nasal gliomas are uncommon congenital lesions arising from abnormal embryonic development. Clinically, these masses are firm and incompressible. Histologically, they are made up of astrocytes and neuroglial cells, embedded in fibrous and vascular connective tissue. Proper management of a nasal glioma requires a multidisciplinary approach including an otorhinolaryngologist, radiologist, and neurosurgeon. Radiological investigations such as computed tomography or magnetic resonance imaging should be performed to exclude intracranial extension. The mainstay of treatment is conservative surgical excision because nasal gliomas are slow-growing, rarely recurrent, and have no malignant potential. We report one case of nasal glioma in a Chinese infant. He had an uncomplicated surgical intervention with a good cosmetic result. A review of the clinical features of and diagnostic approach to nasal gliomas is also presented.

Glioma↗
PubMed2005

Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia.

Deletions from the derivative chromosome 9, der(9), of the translocation, t(9;22)(q34;q11), at the site of the ABL/BCR fusion gene, have been demonstrated by fluorescence in situ hybridisation (FISH), in both Philadelphia chromosome (Ph)-positive chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL). In CML they occur in 10-15% of cases and appear to indicate a worse prognosis, whereas in ALL, the situation is unclear. This study presents the findings of dual fusion FISH used to detect such deletions in a series of 27 BCR/ ABL-positive childhood ALL patients. Metaphase FISH was essential for the accurate interpretation of interphase FISH signal patterns. Three cases (11%) had a single fusion signal, resulting from deletions of the der(9). Three other patients with variant translocations and one with an insertion, also had a single fusion, but with no evidence of deletions. Gain of a fusion in approximately one-third of patients indicated a second Ph, which appears to be a diagnostic marker of Ph-positive ALL. This study shows that the incidence of deletions from the der(9) in childhood ALL is at least as high as that reported for CML.

Child↗
PubMed2005

Snakebite in a child: could we avoid the anaphylaxis or the fasciotomies?

INTRODUCTION: We report the unusual presentation and complications of a case of snakebite, involving a child and his mother, who were bitten by the same snake. CLINICAL PICTURE: The mother was well but the child developed worsening local pain and swelling. TREATMENT AND OUTCOME: Test doses of antivenom were administered but he developed anaphylactic shock. Subsequently, he developed compartment syndrome and fasciotomies were performed. CONCLUSIONS: This report serves to alert the public to a few of the avoidable risk factors associated with snakebites (such as avoiding areas known to harbour snakes in the evening in summer and autumn, and wearing protective footwear), and the clinician of the important management issues in snakebites. Precautions for anaphylaxis must be taken when antivenom is administered. If a bitten patient with rapid extension of local injury does not receive any antivenom, compartment syndrome complicating local injury can occur.

Anaphylaxis↗
PubMed2004

Clinical and endocrine data for goserelin plus anastrozole as second-line endocrine therapy for premenopausal advanced breast cancer.

A total of 16 premenopausal women with metastatic breast cancer (N=13) or locally advanced primary breast cancer (N=3) were treated with a combination of a gonadotropin-releasing hormone agonist goserelin, and a selective aromatase inhibitor anastrozole. All had previously been treated with goserelin and tamoxifen. In all, 12 patients (75%) achieved objective response or durable stable disease at 6 months, with a median duration of remission of 17+ months (range 6-47 months). Four patients still have clinical benefit. Introduction of goserelin and tamoxifen resulted in an 89% reduction in mean oestradiol levels (pretreatment vs 6 months=224 vs 24 pmol l(-1)) (P<0.0001). Substitution of tamoxifen by anastrozole on progression resulted in a further 76% fall (to 6 pmol l(-1) at 3 months) (P<0.0001). Treatment with goserelin and tamoxifen led to a 90% fall in the mean follicle-stimulating hormone (P<0.001). This was reversed once therapy was changed to goserelin and anastrozole. A similar initial reduction was seen in the mean luteinising hormone levels, but substitution of tamoxifen by anastrozole on progression resulted in no significant change. Goserelin and tamoxifen did not lead to any significant change in testosterone and androstenedione levels. The combined use of goserelin and anastrozole as second-line endocrine therapy produces a significant clinical response of worthwhile duration, with demonstrable endocrine changes, in premenopausal women with advanced breast cancer, and offers them another therapeutic option. Further studies involving more patients and longer follow-up are indicated.

Adult↗
PubMed2004

Metastatic carcinoma of the breast with tubular features: differences compared with metastatic ductal carcinoma of no specific type.

AIMS: To compare the metastatic pattern at presentation and the prognosis with metastases of 48 patients with carcinomas with tubular features (45 tubular mixed and three pure tubular) and 302 patients with tumours of ductal of no special type (DNST). MATERIALS AND METHODS: We carried out a retrospective study from a prospectively maintained database of all patients who developed metastatic disease from carcinoma of the breast in Nottingham, U.K., since 1997. We recorded site of first presentation with metastatic disease, radiological features, histological features and characteristics of the primary tumour. RESULTS: The group of patients with tubular features were older at metastatic presentation (63.9 years vs 59.6 years; P=0.012), had a longer disease-free interval (87 months vs 34 months: P<0.001) and a longer survival with metastases (P<0.002). This group were less likely to have liver metastases (23% vs 41%; P=0.028), in particular multiple liver metastases (50% vs 71%; P=0.015) than the patients with DNST. Other factors known to be associated with prolonged survival, such as low histological grade of the primary invasive tumour and positive oestrogen receptor (ER) status, were more common in the group of patients with tumours with tubular features (Grade 1: 33% vs 3%; Grade 2: 42% vs 25%; Grade 3: 25% vs 72%; P<0.001), (ER positivity 76% vs 52%; P=0.009). When patients with grade 2 tumours were compared, the age at metastatic presentation, disease-free interval and the presence of multiple liver metastases were still significantly different between the two groups. CONCLUSION: Patients with metastatic breast carcinoma with tubular features have a longer survival with metastases than patients with metastatic DNST carcinoma. This improved survival can be explained by better well-recognised prognostic features, such as metastatic site pattern, histological grade, ER status and disease-free interval.

Adenocarcinoma↗
PubMed2004

Brain metastases from breast cancer: identification of a high-risk group.

AIMS: Brain metastases from breast cancer are an uncommon initial presentation of metastatic breast cancer, but brain metastases commonly occur later in women's metastatic illness. The aims of this study were to document the type, frequency, and temporal occurrence of brain metastases from breast cancer as well as the survival of women with such metastases, and to attempt to identify a subgroup of women at high risk of brain metastases who may benefit from pre-emptive medical intervention. MATERIALS AND METHODS: The radiological reports of all women presenting with metastases aged under 70 years who had subsequently died were examined. The type, frequency, temporal occurrence and survival with brain metastases were documented. Correlations were sought between the frequency of brain metastases and age at metastatic presentation, tumour grade, histological type and oestrogen receptor (ER) status. RESULTS: Of 219 patients who had died with metastatic disease and who were under 70 years of age at metastatic presentation, 49 (22%) developed brain metastases. The development of brain metastases was related to young age (P = 0.0002), with 43% of women under 40 years developing brain metastases. Brain metastases were more common in women whose tumours were ER negative (38%) compared with women with ER-positive disease (14%) (P = 0.0003). By combining age and ER status, it is possible to identify a group of women (age under 50 years and ER negative) with a 53% risk of developing brain metastases. This group included many women who had chemotherapy for visceral metastases, and 68% had either stable disease or disease response at other sites at the time of brain metastases presentation. CONCLUSION: It is possible to identify a subgroup of women with metastatic breast cancer at high risk of brain metastases who may benefit from pre-emptive medical intervention, such as screening or prophylactic treatment.

Adult↗
PubMed2004

Patterns of metastatic breast carcinoma: influence of tumour histological grade.

AIM: To assess if the pattern of metastatic spread of carcinoma of the breast varies according to tumour histological grade. MATERIALS AND METHODS: The clinical details, histological features of the primary tumour, and imaging findings at presentation of patients with metastatic breast cancer have been recorded prospectively since 1997. The pattern of metastatic spread, age at metastasis, metastasis-free interval (MFI), and length of survival with metastases were analysed by tumour grade. RESULTS: There was a significant association between histological high-grade tumours and high frequency of intra-pulmonary metastases (p=0.013); liver metastases (p=0.039); para-aortic lymphadenopathy (p=0.022) and metastatic presentation under 50 years of age (p=0.003). A significant correlation was also demonstrated between histological low-grade tumours and increased frequency of pleural disease (p=0.020); increased frequency of bone metastases (p=0.004); prolonged MFI (MFI>5 years; p<0.0001); and increased length of survival (p<0.0001). CONCLUSION: There is a correlation between patterns of metastatic spread and tumour histological grade. This partly explains the negative prognostic value of high tumour grade, as metastases from grade 3 tumours more commonly occur at sites associated with a worse prognosis. This finding may also prove useful in interpreting imaging in patients who have a history of breast cancer and undergo subsequent imaging because of new symptoms.

Age Factors↗
PubMed2003

A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population.

BACKGROUND: Colorectal cancer screening by guaiac faecal occult blood test has been shown to reduce the incidence and mortality of colorectal cancer in Western populations. The optimal faecal occult blood test, whether guaiac or immunochemical, for colorectal cancer screening in the Chinese population remains to be defined. AIM: To compare the performance characteristics of a sensitive guaiac-based faecal occult blood test (Hemoccult SENSA) and an immunochemical faecal occult blood test (FlexSure OBT) in a Chinese population referred for colonoscopy. METHODS: One hundred and thirty-five consecutive patients who were referred for colonoscopy and who met the study inclusion criteria took samples for the two faecal occult blood tests simultaneously from three successive stool specimens, with no dietary restrictions. All tests were developed and interpreted by a single experienced technician who was blind to the clinical diagnosis. The sensitivity, specificity and positive predictive value for the detection of colorectal adenomas and cancers were estimated for the two tests. RESULTS: The sensitivity, specificity and positive predictive value for the detection of significant colorectal neoplasia (adenomas > or = 1.0 cm and cancers) were 91%, 70% and 18% for Hemoccult SENSA and 82%, 94% and 47% for FlexSure OBT. The specificity and positive predictive value were significantly higher for FlexSure OBT than for Hemoccult SENSA (P < 0.001 and P = 0.016, respectively). Combining the positive results from both faecal occult blood tests did not improve the accuracy. CONCLUSION: The positive predictive value of the immunochemical faecal occult blood test for the detection of significant colorectal neoplasia was 29% better than that of the sensitive guaiac-based test. This may relate to the Chinese diet and requires further study. The poor specificity of the sensitive guaiac-based test, without dietary restriction, makes it less useful for colorectal cancer screening in a Chinese population.

Adult↗
PubMed2003

Bone metastases from breast carcinoma: histopathological - radiological correlations and prognostic features.

The aim of this study was to identify factors that may be associated with the development of bone metastases in patients with metastatic breast carcinoma and to see if any of these factors had a bearing on subsequent survival. In total, 492 patients presented to the Nottingham City Hospital with metastatic breast carcinoma between July 1997 and December 2001. Of these, 267 patients had bone metastases at presentation with metastatic disease, 91 patients in this group had bone as their only site of metastatic disease. Sites of first presentation of metastatic disease were prospectively recorded, as were histological features of the primary tumour (tumour type, histological grade, lymph node stage, tumour size and oestrogen receptor (ER) status). The radiological features of the bone metastases, the metastasis-free interval and serological tumour marker levels at presentation with metastases were all recorded. There was a significant association between the development of bone metastases and lower grade tumours (P=0.019), ER-positive tumours (P<0.0001) and the lymph node stage of the primary tumour (P=0.047). A multivariate analysis found that metastasis-free interval, additional sites of metastatic disease other than bone, ER status and serological tumour marker levels all independently contributed to survival from time of presentation with bone metastases.

Adult↗
PubMed2003

Prognostic factors for patients with hepatic metastases from breast cancer.

Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

Adult↗
PubMed2003

A genomic approach to mutation analysis of holocarboxylase synthetase gene in three Chinese patients with late-onset holocarboxylase synthetase deficiency.

OBJECTIVE: Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10). Patients commonly present during early infancy with acute metabolic derangements and severe metabolic acidosis. Recently, a late onset form of HLCS deficiency was also described. The different phenotypes (early and late presenting) may be related to a spectrum of mutations in HLCS gene. Applications of mutation analysis in HLCS had been limited previously by the requirement of cDNA from living tissue for study. We described here a genomic approach for molecular diagnosis of HLCS deficiency which we have used to detect mutations in Chinese patients who had the late-onset form of HLCS deficiency. In addition, a fibroblast cell line with MCD from Coriell Cell repositories was also studied. DESIGN AND METHODS: Three Chinese patients with late onset HLCS deficiency were studied. The genomic sequence of HLCS was retrieved and newly designed primers were used to cover all coding sequences of the gene. PCR products were analyzed by direct sequencing. Population allelic frequencies of mutations detected were determined by genotyping of control samples by restriction fragment length polymorphism. RESULTS: We found a recurrent mutation, R508W, in the three unrelated Chinese patients. Two were homozygous for this mutation. The other patient was a compound heterozygote of R508W and a novel mutation, D634N. The results suggest that R508W may be an important and relatively prevalent disease-causing mutation in Chinese MCD patients. A fibroblast cell-line from an African patient revealed an additional novel mutation, R565X and a known mutation, V550M. CONCLUSION: R508W is a recurrent mutation in Chinese MCD patients which is associated with the late onset phenotype. This new genomic approach for mutation analysis of HLCS gene provides new opportunities in studies of MCD.

Asian People↗